Abstract: Diffuse pediatric-type high-grade glioma (pHGG), RTK1 subtype, is an uncommon aggressive tumor affecting both children and adults. We describe the case of a 66-year-old woman who presented with a left frontal lobe mass. Following surgical resection, the patient developed herpes simplex virus 2 meningoencephalitis, resulting in death. Histological examination revealed a high-grade glioma demonstrating nuclear pleomorphism, high mitotic activity, vascular proliferation and necrosis. The tumor also exhibited oligodendroglial-like features, nuclear clusters and small true rosette-like structures. Genetic analysis identified partial arm 1p loss and 19q loss, PDGFRA, MYCN and MDM4 amplification, an ATRX mutation and a novel SYN2::PPARG fusion. Homozygous CDKN2A/B deletion was also present. Genomic DNA methylation profiling matched diffuse pediatric-type high-grade glioma, RTK1 subtype, subclass C. This case underscores the importance of utilizing advanced molecular and genomic techniques for accurately diagnosing glial tumors. Further study of the SYN2::PPARG fusion in gliomas could potentially offer insights into its role in glioma biology and possibly help elucidate therapeutic strategies for tumors with PPARG fusions.
Article highlights: We report a case of diffuse pediatric-type high-grade glioma (pHGG), RTK1 subtype, subclass C in an adult confirmed by genomic DNA methylation analysis. The tumor demonstrated PDGFRA, MYCN and MDM4 amplification, and ATRX and KIT pathogenic mutations. The tumor also harbored a SYN2::PPARG gene fusion not previously reported in glioma. The case illustrates the importance of integrating advanced molecular techniques into the diagnostic process for older patients with atypical presentations of high-grade glioma. The potential biological significance and possible future therapeutic implications of the SYN2::PPARG gene fusion are discussed.
Keywords: ATRX mutation; Diffuse pediatric-type high-grade glioma; MDM4 amplification; MYCN amplification; PDGFRA amplification; RTK1 subtype; SYN2::PPARG gene fusion; genomic DNA methylation analysis; subclass C.